James W. Mandell, M.D., Ph.D.
Associate Professor of Pathology
EDUCATION:
Medical School: Cornell University Medical College,
New York, NY. MD, 1992; Ph.D, 1991 M.D./Ph.D.
Graduate School: Postdoctoral Neuroscience,
University of Virginia, 1992 - 1994
Residency: Anatomic Pathology, University of
Virginia, 1994 - 1995
1995 - 1996 Chief Resident, Anatomic Pathology, University
of Virginia
Fellowship: Fellow, Neuropathology, University of
Virginia, 1996 - 1998
CLINICAL:
Diagnostic neuropathology of neuromuscular disorders,
neurodegenerative disease, nervous system neoplasms. See my
neuromuscular pathology site.
RESEARCH:
- Signal transduction mechanisms underlying the astroglial response
to neuronal injury and degeneration
- Roles of astrocytes and other glia in the recognition and
phagocytic clearance of degenerating neurons, axons, and synapses
during development and degeneration
Astrocytes play an active role in the central nervous system's
response to many forms of neural injury and neurodegenerative disease.
The underlying mechanisms and functional consequences of this cellular
response are poorly understood. My laboratory investigates
transmembrane signaling pathways important for the astroglial response
to neuronal injury. A recent focus is on the recognition
and clearance of apoptotic/degenerating neurons during development and
degeneration, which is mediated in part by the
BAI1/DOCK/ELMO/Rac1 engulfment pathway. We utilize techniques of
cellular and molecular neuroscience to elucidate the intracellular
signal transduction mechanisms and cell biological machinery
involved in these processes. Specific techniques include generation and
phenotypic analysis of conditional knockout mice, primary neuronal and
glial culture and coculture, DNA transfection, promoter/reporter
assays, immunohistochemistry, electron microscopy, and protein
and nucleic acid blotting.
More information on my research laboratory.
Evidence for astroglial engulfment of degenerating axons in the
adult mouse olfactory bulb. Olfactory sensory neuron axons were
labeled (red) via anterograde transport of the MiniRuby dye, and
astroglia are labeled with anti-GFAP (green). No uptake is
evident in intact glomeruli (A), but astroglial engulfment is observed
in glomeruli showing fragmented axonal degeneration (B).
REFERENCES:
- Correa-Cerro LS, Mandell JW. Molecular mechanisms
of astrogliosis: new approaches with mouse genetics.
J Neuropathol Exp Neurol. 2007 66(3):169-76.
Review.
- Favero CB and Mandell JW*. A pharmacological
activator of AMP-activated kinase induces astrocyte stellation".
Brain Research 2007 1168:1-10
- Park, D., A.C. Tosello-Trampont, M.R. Elliott, Z. Ma, M. Lu, L.
Haney, J.W. Mandell, A. Klibanov, K.S. Ravichandran.
2007. BAI1 is an engulfment receptor for apoptotic cells upstream of
the ELMO/Dock180/Rac module. Nature. 2007
450:430-4.
- Mandell JW*. Immunohistochemical assessment of
protein phosphorylation state: the dream and the reality.
Histochem Cell Biol. 2008
Sep;130(3):465-71.
- Swerdlow RH, Miller BB, Lopes MB, Mandell JW,
Wooten GF, Damgaard P, Manning C, Fowler M, Brashear HR. Autosomal
dominant subcortical gliosis presenting as frontotemporal dementia.
Neurology. 2009 72:260-7.
- Mandell JW*, Locke CN; George Glass G,Gianchandani
EP, Bourne TD, Schiff D, Amos S, Papin JA Dephosphorylation of
beta-arrestin 1 in glioblastomas.J. Neuropath. Exp.
Neurol. 2009 68:535-41
- Glass G, Papin JA, Mandell JW*.
SIMPLE: A Sequential Immunoperoxidase Labeling and Erasing
Method. J. Histochem. Cytochem. 2009
Apr 13. [Epub ahead of print].
- Heffron DS, Landreth GE, Samuels IS, Mandell JW*.
Brain-Specific Deletion Of ERK2 MAP Kinase Leads to Aberrant Cortical
Collagen Deposition. Am. J. Pathol.
2009, in revision
Neuroscience
Graduate Program
A more complete list of Dr. Mandell's publications
can be obtained from
PubMed
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